Reducing toxicity and increasing efficiency: aconitine with liquiritin and glycyrrhetinic acid regulate calcium regulatory proteins in rat myocardial cell

Background: Compatibility of Radix Aconiti Carmichaeli and Liquorice is known to treat heart diseases such as heart failure and cardiac arrhythmias. This work answers the question that whether the active components (Aconitine, Liquiritin and Glycyrrhetinic Acid) of Radix Aconiti Carmichaeli and Liquorice could result in regulating intracellular calcium homeostasis and calcium cycling, and thereby verifies the therapeutic material basis.Materials and Methods: The myocardial cells were divided into twelve groups randomly as control group, Aconitine group, nine different dose groups that orthogonal combined with Aconitine, Liquiritin and Glycyrrhetinic Acid, and Verapamil group. The myocardial cellular survival rate and morphology were assessed. The expression of calcium regulation protein(RyR2、NCX1、DHPR-a1) in the myocardial cell by Western-blotting.Results: The results exhibited that Aconitine (120 uM) significantly damaged on myocardial cell, decreased the survival rate and expression of Na+/Ca2+ exchangers (NCX1) and dihydropteridine reducta-α1 (DHPR-a1), and increased the expression of ryanodine receptor type2 (RyR2) obviously. The compatibility groups (Aconitine, Liquiritin and Glycyrrhetinic Acid) all could against the damage on the myocardial cell by Aconitine at different levels.Conclusion: Aconitine with Liquiritin and Glycyrrhetinic Acid may regulate the expression of calcium-regulated proteins to protect myocardial cells from damage.Keywords: Aconitine, Liquiritin, Glycyrrhetinic Acid, myocardial cell, calcium regulator

Hyperoxalemia Leads to Oxidative Stress in Endothelial Cells and Mice with Chronic Kidney Disease

Introduction: Cardiovascular disease is the most common cause of morbidity and mortality in patients with ESRD. In addition to phosphate overload, oxalate, a common uremic toxin, is also involved in vascular calcification in patients with ESRD. The present study investigated the role and mechanism of hyperoxalemia in vascular calcification in mice with uremia. Methods: A uremic atherosclerosis (UA) model was established by left renal excision and right renal electrocoagulation in apoE−/− mice to investigate the relationship between oxalate loading and vascular calcification. After 12 weeks, serum and vascular levels of oxalate, vascular calcification, inflammatory factors (TNF-α and IL-6), oxidative stress markers (malondialdehyde [MDA], and advanced oxidation protein products [AOPP]) were assessed in UA mice. The oral oxalate-degrading microbe Oxalobacter formigenes (O. formigenes) was used to evaluate the effect of a reduction in oxalate levels on vascular calcification. The mechanism underlying the effect of oxalate loading on vascular calcification was assessed in cultured human aortic endothelial cells (HAECs) and human aortic smooth muscle cells (HASMCs). Results: Serum oxalate levels were significantly increased in UA mice. Compared to the control mice, UA mice developed more areas of aortic calcification and showed significant increases in aortic oxalate levels and serum levels of oxidative stress markers and inflammatory factors. The correlation analysis showed that serum oxalate levels were positively correlated with the vascular oxalate levels and serum MDA, AOPP, and TNF-α levels, and negatively correlated with superoxide dismutase activity. The O. formigenes intervention decreased serum and vascular oxalate levels, while did not improve vascular calcification significantly. In addition, systemic inflammation and oxidative stress were also improved in the O. formigenes group. In vitro, high concentrations of oxalate dose-dependently increased oxidative stress and inflammatory factor expression in HAECs, but not in HASMCs. Conclusions: Our results indicated that hyperoxalemia led to the systemic inflammation and the activation of oxidative stress. The reduction in oxalate levels by O. formigenes might be a promising treatment for the prevention of oxalate deposition in calcified areas of patients with ESRD

Human immunodeficiency virus type 1 specific cytotoxic T lymphocyte responses in Chinese infected with HIV-1 B'/C Recombinant (CRF07_BC)

<p>Abstract</p> <p>Background</p> <p>The characterization of HIV-1-specific T cell responses in people infected with locally circulating HIV-1 strain will facilitate the development of HIV-1 vaccine. Sixty intravenous drug users infected with HIV-1 circulating recombinant form 07_BC (CRF07_BC), which has been spreading rapidly in western China from north to south, were recruited from Xinjiang, China to assess the HIV-1-specific T cell responses at single peptide level with overlapping peptides (OLP) covering the whole concensus clades B and C proteome.</p> <p>Results</p> <p>The median of the total magnitude and total number of OLPs recognized by CTL responses were 10925 SFC/million PBMC and 25 OLPs, respectively, when tested by clade C peptides, which was significantly higher than when tested by clade B peptides. The immunodominant regions, which cover 14% (58/413) of the HIV-1 proteome, are widely distributed throughout the HIV-1 proteome except in Tat, Vpu and Pol-PR, with Gag, Pol-RT, Pol-Int and Nef being most frequently targeted. The subdominant epitopes are mostly located in p24, Nef, integrase, Vpr and Vif. Of the responses directed to clade C OLPs, 61.75% (972/1574) can be observed when tested with corresponding clade B OLPs. However, Pol-PR and Vpu tend to be targeted in the clade B sequence rather than the clade C sequence, which is in line with the recombinant pattern of CRF07_BC. Stronger and broader CTL responses in subjects with CD4 cell counts ranging from 200 to 400/mm³were observed when compared to those with less than 200/mm³or more than 400/mm³, though there have been no significant correlations identified between the accumulative CTL responses or overall breadth and CD4 cell count or plasma viral load.</p> <p>Conclusion</p> <p>This is the first study conducted to comprehensively address T cell responses in Chinese subjects infected with HIV-1 CRF07_BC in which subtle differences in cross-reactivity were observed, though similar patterns of overall immune responses were demonstrated with clade B infected populations. The immunodominant regions identified in this population can facilitate future HIV-1 vaccine development in China.</p

Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): A prospective multicenter diagnostic cohort study

Background: After neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer, high pathologically complete response (pCR) rates are being achieved especially in patients with squamous cell carcinoma (SCC). An active surveillance strategy has been proposed for SCC patients with clinically complete response (cCR) after nCRT. To justify omitting surgical resection, patients with residual disease should be accurately identified. The aim of this study is to assess the accuracy of response evaluations after nCRT based on the preSANO trial, including positron emission tomography with computed tomography (PET-CT), endoscopy with bite-on-bite biopsies and endoscopic ultrasonography (EUS) with fine-needle aspiration (FNA) in patients with potentially curable esophageal SCC. Methods: Operable esophageal SCC patients who are planned to undergo nCRT according to the CROSS regimen and are planned to undergo surgery will be recruited from four Asian centers. Four to 6 weeks after completion of nCRT, patients will undergo a first clinical response evaluation (CRE-1) consisting of endoscopy with bite-on-bite biopsies. In patients without histological evidence of residual tumor (i.e. without positive biopsies), surgery will be postponed another 6 weeks. A second clinical response evaluation (CRE-2) will be performed 10-12 weeks after completion of nCRT, consisting of PET-CT, endoscopy with bite-on-bite biopsies and EUS with FNA. Immediately after CRE-2 all patients without evidence of distant metastases will undergo esophagectomy. Results of CRE-1 and CRE-2 as well as results of the three single diagnostic modalities will be correlated to pathological response in the resection specimen (gold standard) for calculation of sensitivity, specificity, negative predictive value and positive predictive value. Discussion: If the current study shows that major locoregional residual disease (> 10% residual carcinoma or any residual nodal disease) can be accurately (i.e. with sensitivity of 80.5%) detected in patients with esophageal SCC, a prospective trial will be conducted comparing active surveillance with standard esophagectomy in patients with a clinically complete response after nCRT (SINO trial). Trial registration: The preSINO trial has been registered at ClinicalTrials.gov as NCT03937362 (May 3, 2019)

Additional file 1 of Identification of breast cancer subgroups and immune characterization based on glutamine metabolism-related genes

Supplementary Material

Exterior and Internal Uniform Loading of Pt Nanoparticles on Yolk-Shell La2O3 by Acoustic Levitation Synthesis with Enhanced Photocatalytic Performance

By the deposition of noble metal nanoparticles on a metal oxide substrate with a specific micro-/nanostructure, namely, yolk-shell structure, a remarkable improvement in photocatalytic performance can be achieved by the composites. Nevertheless, noble metal nanoparticles only distribute on the surface shell of metal oxide substrates when the conventional wet-chemistry reduction approach is employed. Herein, we proposed a novel acoustic levitation synthesis of Pt nanoparticles deposited on yolk-shell La2O3. The composites not only displayed well-defined, homogeneous distribution of Pt NPs on the exterior shell of La2O3 and the interior La2O3 core, but an enhanced chemical interaction between Pt and La2O3. The unique structure not only can display improved photocatalytic degradation rate toward methyl orange, but also may show great potential in fields of hydrogen generation, environmental protection, etc. The novel acoustic levitation synthesis can supplement the methodology of synthesizing well dispersed noble metal oxides over the whole yolk-shell structure through noble metal NPs deposition method

Fast Synthesis of Pt Nanocrystals and Pt/Microporous La2O3 Materials Using Acoustic Levitation

Abstract Usually, we must use an appropriate support material to keep the metal species stable and finely dispersed as supported metal nanoparticles for industry application. Therefore, the choice of support material is a key factor in determining the dispersion and particle size of the noble metal species. Here, we report the synthesis of a single-atom Pt material in the solution and supported Pt nanoclusters on microporous La2O3 by a one-step acoustic levitation method without any pretreatment/modification of raw oxide. We have strongly contributed to the synthetic methodology of the surface/interfacial heterogeneous catalysts in this study, and this finding could open another door for synthesis of supported metal nanoparticles on porous materials for environmental catalysis

Cooling and Wetting Effects of Agricultural Development on Near-Surface Atmosphere over Northeast China

The effects of agricultural development on observed changes in near-surface atmospheric temperature and moisture from 1960 to 2014 over Northeast China are evaluated using data from 109 meteorological stations. Cultivated land fraction (CF) within a 3 km radius of the meteorological station is used as a quantitative indicator of agricultural intensity. Stations with large CFs experience a less significant increase in air temperature, especially in daily maximum temperature (Tmax) and a more rapid increase in vapor pressure (ea) and relative humidity (RH) than stations with small CFs, especially during the main growing season (from May to September). Compared with the reference station group with CF<0.2, cooling effects during May to September in terms of daily mean, maximum, and minimum temperature by −0.067°C, −0.081°C, and −0.069°C per decade and wetting effects of May to September regarding ea by 0.075 hPa and RH by 0.56% per decade exist for the station group with CF>0.5. The cooling and wetting effects can be attributed to the agricultural development and thus should be considered when analyzing the near-surface atmospheric temperature and moisture records in Northeast China

Temporal Variation of Chlorophyll-a Concentrations in Highly Dynamic Waters from Unattended Sensors and Remote Sensing Observations

Monitoring of water quality changes in highly dynamic inland lakes is frequently impeded by insufficient spatial and temporal coverage, for both field surveys and remote sensing methods. To track short-term variations of chlorophyll fluorescence and chlorophyll-a concentrations in Poyang Lake, the largest freshwater lake in China, high-frequency, in-situ, measurements were collected from two fixed stations. The K-mean clustering method was also applied to identify clusters with similar spatio-temporal variations, using remote sensing Chl-a data products from the MERIS satellite, taken from 2003 to 2012. Four lake area classes were obtained with distinct spatio-temporal patterns, two of which were selected for in situ measurement. Distinct daily periodic variations were observed, with peaks at approximately 3:00 PM and troughs at night or early morning. Short-term variations of chlorophyll fluorescence and Chl-a levels were revealed, with a maximum intra-diurnal ratio of 5.1 and inter-diurnal ratio of 7.4, respectively. Using geostatistical analysis, the temporal range of chlorophyll fluorescence and corresponding Chl-a variations was determined to be 9.6 h, which indicates that there is a temporal discrepancy between Chl-a variations and the sampling frequency of current satellite missions. An analysis of the optimal sampling strategies demonstrated that the influence of the sampling time on the mean Chl-a concentrations observed was higher than 25%, and the uncertainty of any single Terra/MODIS or Aqua/MODIS observation was approximately 15%. Therefore, sampling twice a day is essential to resolve Chl-a variations with a bias level of 10% or less. The results highlight short-term variations of critical water quality parameters in freshwater, and they help identify specific design requirements for geostationary earth observation missions, so that they can better address the challenges of monitoring complex coastal and inland environments around the world